科研之友
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摘要
The role of estrogen receptor alpha (ERa) in breast cancer has been studied extensively, and its protein expression is prognostic and a primary determinant of endocrine sensitivity. However, much less is known about the role of ER beta and its relevance remains unclear due to the publication of conflicting reports. Here, we provide evidence that much of this controversy may be explained by variability in antibody sensitivity and specificity and describe the development, characterization, and potential applications of a novel monoclonal antibody targeting full-length human ER beta and its splice variant forms. Specifically, we demonstrate that a number of commercially available ER beta antibodies are insensitive for ER beta and exhibit significant cross-reaction with ERa. However, our newly developed MC10 ER beta antibody is shown to be highly specific and sensitive for detection of full-length ER beta and its variant forms. Strong and variable staining patterns for endogenous levels of ER beta protein were detected in normal human tissues and breast tumors using the MC10 antibody. Importantly, ER beta was shown to be expressed in a limited cohort of both ERa positive and ERa negative breast tumors. Taken together, these data demonstrate that the use of poorly validated ER beta antibodies is likely to explain much of the controversy in the field with regard to the biological relevance of ER beta in breast cancer. The use of the MC10 antibody, in combination with highly specific antibodies targeting only full-length ER beta, is likely to provide additional discriminatory features in breast cancers that may be useful in predicting response to therapy. J. Cell. Biochem. 113: 711723, 2012.
- 出版日期2012-2
